Significant challenges are presented by the use of non-autologous tissue in bioprosthetic implants. Chief among the challenges are immunological rejection and/or calcification of the bioprosthetic implant which, in turn, results in the undesirable degradation and stiffening of the tissue. Immunological rejection and calcification are particularly problematic for bioprosthetic heart valves, as calcification of these leaflets after implantation will adversely affect the leaflets' ability to maintain the required one-way flow of blood, i.e., prevent undesirable leaking or regurgitation of blood.
Glutaraldehyde has long been the reagent of choice for cross-linking biological tissues and, more particularly, for cross-linking pericardial tissue used for heart valves. Glutaraldehyde chemically modifies and cross-links collagen to render the biological tissue immunologically acceptable in the human host and stabilize the tissue. While glutaraldehyde remains the preferred cross-linking reagent, it is not without its disadvantages. Indeed, glutaraldehyde has been reported to accelerate the calcification process, which is the main cause of long-term failure in glutaraldehyde-fixed pericardial valves. Furthermore, as glutaraldehyde is cytotoxic and prevents host cell attachment, migration and proliferation, it hinders the ability of treated tissue to regenerate in vivo. Glutaraldehyde also has a tendency to polymerize and to produce undesired side reactions. The types of reactions that are implicated by glutaraldehyde are often difficult to control.
What is therefore needed are strategies that can be used in place of or in conjunction with glutaraldehyde fixation that mitigate some of the disadvantages of glutaraldehyde-treated bioprosthetic tissue.